小细胞肺癌NCCN指南2017第3版 讨论 诊断 病理学

Diagnosis 诊断

Screening 筛检

Ideally, a screening test should detect disease at an early stage when it is still curable.
理想情况下，筛查应检出早期仍可治愈的疾病。

Currently, no effective screening test is available to detect early-stage SCLC; the disease is typically diagnosed when patients present with symptoms indicative of advanced-stage disease.山东省肿瘤医院呼吸肿瘤内科张品良
目前，没有有效的筛选检查可以检出早期小细胞肺癌；通常是当患者出现晚期疾病症状时才确诊。

The National Lung Screening Trial (NLST) reported that screening with annual, low-dose, spiral CT scans decreased lung cancer–specific mortality in asymptomatic high-risk individuals (see the NCCN Guidelines for Lung Cancer Screening, available at NCCN.org).
国家肺癌筛查试验（NLST）报道，每年1次低剂量螺旋CT扫描筛查，在无症状高危个体中肺癌特异性死亡率下降（见NCCN肺癌筛查指南，可在NCCN.org获得）。

Although low-dose CT screening can detect early-stage non-small cell lung cancer (NSCLC), it does not seem to be useful for detecting early-stage SCLC.
虽然低剂量CT筛检可以发现早期非小细胞肺癌（NSCLC），但似乎对检出早期小细胞肺癌没有用。

Low-dose CT screening is probably not useful because of the aggressiveness of SCLC, which results in the development of symptomatic disease between annual scans, thereby limiting the potential effect on mortality.
低剂量CT筛检可能没有用是因为小细胞肺癌的侵袭性，导致在每年1次的检查之间发展为有症状的疾病，因此限制了对死亡率的潜在影响。

Manifestations 表现

SCLC typically presents as a large hilar mass and bulky mediastinal lymphadenopathy that cause cough and dyspnea.
小细胞肺癌的典型表现为肺门大肿块和纵隔巨大淋巴结，引起咳嗽和呼吸困难。

Frequently, patients present with symptoms of widespread metastatic disease, such as weight loss, debility, bone pain, and neurologic compromise.
患者常常出现广泛的转移性疾病症状，如体重减轻、乏力、骨痛和神经损害。

It is uncommon for patients to present with a solitary peripheral nodule without central adenopathy.
无中央淋巴结的孤立性周围型结节患者罕见。

In this situation, fine-needle aspiration (FNA) may not adequately differentiate small cell carcinoma (which is a high-grade neuroendocrine carcinoma) from low-grade (typical carcinoid), intermediate-grade (atypical carcinoid), or large-cell neuroendocrine carcinoma (LCNEC) (which is also a high-grade neuroendocrine carcinoma) (see Lung Neuroendocrine Tumors in the NCCN Guidelines for Neuroendocrine Tumors available at NCCN.org).
在这种情况下，细针穿刺抽吸（FNA）或许不能充分地区分小细胞癌（这是一种高级别的神经内分泌癌）、低级别（典型类癌）、中等级别（不典型类癌）或大细胞神经内分泌癌（LCNEC）（这也是一种高级别神经内分泌癌）（见神经内分泌肿瘤NCC指南中的肺神经内分泌肿瘤，可在NCCN.org获得）。

Many neurologic and endocrine paraneoplastic syndromes are associated with SCLC.
许多神经系统和内分泌副肿瘤综合征与小细胞肺癌有关。

Neurologic syndromes include Lambert-Eaton myasthenic syndrome, encephalomyelitis, and sensory neuropathy.
神经系统症状包括兰伯特-伊顿肌无力综合征、脑脊髓炎以及感觉神经病变。

Patients with the Lambert-Eaton syndrome present with proximal leg weakness that is caused by antibodies directed against the voltage-gated calcium channels.
有兰伯特-伊顿综合征（类重症肌无力综合征）的患者表现为近端下肢无力，是由抗电压门控钙通道抗体引起的。

Paraneoplastic encephalomyelitis and sensory neuropathy are caused by the production of an antibody (anti-Hu) that cross-reacts with both small cell carcinoma antigens and human neuronal RNA-binding proteins resulting in multiple neurologic deficits.
副肿瘤性脑脊髓炎和感觉神经病变是由一种抗体（抗-Hu）引起的，该抗体既能与小细胞癌抗原结合，又能与人神经元RNA结合蛋白相互作用导致多神经损伤。

SCLC cells sometimes produce polypeptide hormones, including vasopressin (antidiuretic hormone [ADH]) and adrenocorticotropic hormone (ACTH), which cause hyponatremia of malignancy (ie, syndrome of inappropriate ADH secretion [SIADH]) and Cushing syndrome, respectively.
小细胞肺癌细胞有时会产生多肽激素，包括加压素（抗利尿激素[ ADH ]）和促肾上腺皮质激素（ACTH），分别引起恶性低钠血症（即抗利尿激素分泌异常综合征[SIADH ]）和库欣综合征。

In patients with SCLC, SIADH occurs more frequently than Cushing syndrome.
在小细胞肺癌患者中，抗利尿激素分泌异常综合征（SIADH）比库欣综合征更常见。

Cancer treatment and/or supportive care may also cause hyponatremia (eg, cisplatin, opiates).
癌症治疗和/或支持治疗也可能导致低钠血症（如顺铂、阿片类）。

Treatment for SIADH includes fluid restriction (which is difficult for patients because of increased thirst), demeclocycline, or vasopressin receptor inhibitors (ie, conivaptan, tolvaptan) (see Principles of Supportive Care in the NCCN Guidelines for SCLC).
抗利尿激素分泌异常综合征（SIADH）的治疗包括限制液体（因为口渴，这对患者是困难的）、地美环素或加压素受体抑制剂（即考尼伐坦、托伐普坦）（见小细胞肺癌NCCN指南中支持治疗的原则）。

ADH levels and hyponatremia usually improve after successful treatment for SCLC.
在小细胞肺癌治疗成功后，ADH（抗利尿激素）水平与低钠血症通常改善。

Pathology 病理学

SCLC is a malignant epithelial tumor consisting of small cells with scant cytoplasm, ill-defined cell borders, finely granular nuclear chromatin, and absent or inconspicuous nucleoli.
小细胞肺癌是一种恶性上皮性肿瘤，由缺乏细胞质的小细胞组成，细胞边界不清、核染色质细颗粒状、核仁缺乏或不明显。

The cells are round, oval, or spindle-shaped; nuclear molding is prominent.
细胞圆形、椭圆形或梭形；核型显著。

The mitotic count is high.
有丝分裂计数高。

The classic and distinctive histology on hematoxylin and eosin (H&E) may be sufficient for identifying SCLC; it is a poorly differentiated tumor that is categorized as a high-grade neuroendocrine carcinoma.
典型且独特的苏木精和伊红（H&E）组织学能够足以识别小细胞肺癌；它是一种低分化肿瘤，归类为一种高级别的神经内分泌癌。

Up to 30% of autopsies in patients with SCLC reveal areas of NSCLC differentiation; this finding is more commonly detected in specimens from previously treated patients and suggests that pulmonary carcinogenesis occurs in a pluripotent stem cell capable of differentiation along divergent pathways.
小细胞肺癌患者中尸检高达30%显示非小细胞肺癌分化区域；在既往治疗过的患者标本中更常检出这一发现，因此认为，肺癌发生在一个能沿不同途径分化的多能干细胞。

Although 95% of small cell carcinomas originate in the lung, they can also arise from extrapulmonary sites, including the nasopharynx, gastrointestinal tract, and genitourinary tract.
虽然95%的小细胞癌起源于肺，但也可以起源于肺外部位，包括鼻咽、胃肠道和泌尿生殖道。

Both pulmonary and extrapulmonary small cell carcinomas have a similar clinical and biologic behavior, leading to a high potential for widespread metastases.
肺和肺外小细胞癌两者均有相似的临床和生物学行为，广泛转移的潜能高。

Nearly all SCLCs are immunoreactive for keratin, epithelial membrane antigen, and thyroid transcription factor–1 (TTF-1).
几乎所有的小细胞肺癌对角蛋白、上皮膜抗原和甲状腺转录因子-1（TTF-1）免疫反应阳性。

Most SCLCs also stain positively for markers of neuroendocrine differentiation, including chromogranin A, neuron-specific enolase, neural cell adhesion molecule (NCAM; CD56), and synaptophysin.
对于神经内分泌分化的标记，包括嗜铬粒蛋白A、神经元特异性烯醇化酶、神经细胞黏附分子（NCAM；CD56）和突触素，大部分小细胞肺癌染色也是阳性的。

However, these markers alone cannot be used to distinguish SCLC from NSCLC, because approximately 10% of NSCLCs will be immunoreactive for at least one of these neuroendocrine markers.
然而，这些标记不能用来区分小细胞肺癌和非小细胞肺癌，因为大约10%的NSCLC这些神经内分泌标记至少有一个阳性。